In a conventional method of producing a pharmaceutical tablet, a mixture containing the biologically active ingredient together with diluents such as lactose and other ingredients is mixed and portions of the mixture are formed into discrete tablets by, for example, pressing samples of the mixture.
The resulting tablet core may be coated using, for example, a conventional liquid coating technique in which the tablet cores are tumbled in a drum while liquid coating material is sprayed onto the surfaces of the tablet cores. The liquid coating on the surfaces of the cores is usually dried by heating to dry the coating.
A problem with the method of producing tablets described above is that, due to inhomogeneity of the mixture from which the tablet cores are made, the amount of active ingredient in the resulting tablet cores varies from one tablet to the next. While that is a problem for all types of tablet core produced in that way, it is a particularly serious problem when the amount of active ingredient in each core is low, for example for active compounds of high activity. In that case a small absolute variation in the percentage amount of active ingredient in the cores corresponds to a significant variation in the dose contained in each tablet which is clearly most undesirable.
Various solutions to that problem have been proposed.
In one method, the active ingredient and a small amount of diluent are granulated together and the granulated mixture is added to further diluent. The mixture is then compressed in the usual way to form tablet cores. Using that method, at each stage the proportion of active ingredient added to the diluent is high thus helping to reduce the variation in the dose in each tablet core. However, the variation in the dose for tablets formed by this method is still found to be as much as ±15%.
In an alternative known method, a two-layer tablet core is produced by compressing a powder having a lower layer of diluent and an upper layer of diluent mixed with the active ingredient. Cores formed by this method, however, require special designs of presses and are found to have a relatively large variation in their contained dose. They also require reformulation of the components making up the core. Also, such presses generally have lower rates of production of cores than standard presses.
In another known method, a coating solution containing active material is applied to the surfaces of small beads using conventional spray coating techniques, for example by spraying the coating solution towards the beads as they are tumbled in a revolving drum. The coated beads are filled into capsule shells for administration. Such a method is not appropriate for use where accuracy in the amount of the active material applied to the cores is required because there is little control over the amount of coating material applied to each core using that method.